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The Lipid Bilayer
Separates intracellular spaces from the outside environment
Regulates exchange within a cell
Naturally impermeable to most molecules
Cell Membrane Characteristics
Not a rigid barrier, but a living structure
Functions:
Evaluate and communicate with the environment
Acquire needed molecules & discard unnecessary ones
Traverse its environment
Internal Membranes & Compartmentalization
Organelles isolated by their own membranes
Allows different reactions to occur in separate regions
Examples:
ER: Lipid sorting, membrane-bound/secreted protein synthesis
Peroxisome: Oxidation of long fatty acids
Lysosome: Hydrolysis of macromolecules
Golgi: Protein modification & trafficking
Mitochondria: RedOx reactions, energy extraction
Membrane Composition
Consists of phospholipids and proteins
Some proteins act as rafts isolating specific regions
Amphipathic nature helps form bilayers in water
Phospholipid Behavior in Bilayers
Dynamic positioning:
Lateral diffusion
Flexion
Rotation
Flip-flop (facilitated by flippase)
Membrane Fluidity
Function of temperature & composition
More unsaturated lipids = increased fluidity
Cholesterol buffers fluidity against temperature changes
Membrane Assembly
Begins in the ER
Phospholipids synthesized in the cytosol, inserted into ER membrane
Scramblase randomizes lipid distribution in the ER
Asymmetric Lipid Distribution
Occurs at the Golgi
Maintains orientation during transport
Glycolipids positioned on extracellular leaflet
Phosphatidylserine flips to extracellular leaflet during apoptosis
Membrane Proteins & Functions
Types:
Transporters
Anchors
Receptors
Enzymes
Membrane Protein Association
Integral:
Transmembrane
Monolayer-associated lipid-linked
Peripheral:
Protein-attached
Membrane-Spanning Protein Domains
Rich in hydrophobic residues
Form alpha-helices or beta-sheets
Hydrophilic regions create aqueous pores
Studying Membrane Proteins
Detergents can release membrane proteins
Methods:
X-ray crystallography
Cryo-electron microscopy
NMR spectroscopy
Example: Bacteriorhodopsin (light-driven proton pump)
The Cell Cortex
Network of proteins supporting cell shape
Cytoskeleton attachment to membrane proteins
Actin complexes linked by spectrin tetramers
Membrane Protein Movement
Measured by FRAP (Fluorescence Recovery After Photobleaching)
Types:
Unrestricted
Confined
Tethered
Protein Movement Restriction Mechanisms
Tethering to intracellular/extracellular proteins
Interactions with adjacent cells
Diffusion barriers at tight junctions
Epithelial Cell Polarity
Tight junctions create diffusion barriers
Separate apical & basolateral domains
Glycosylation & Cell Recognition
Plasma membrane coated with sugars
Glycosylation occurs on:
Lipids
Transmembrane proteins
Peripheral proteins
Proteoglycans contain glycosaminoglycans (GAGs)
Role of Glycocalyx
Protects cells from damage
Facilitates cell recognition
Inflammatory responses involve lectins binding to glycosylated cells
Experimental Techniques
Purified proteins inserted into artificial bilayers to study function
Liposomes useful for studying transport proteins